Transient circuits in development

It turns out that the young brain is structurally different from the adult brain. For example before and during the critical period a transient neuronal circuit is present in cortex. This circuit is formed by subplate neurons (SP) (see fig. on right). These neurons receive thalamic inputs and our recent work shows that they provide excitatory input to cortical layer 4, the ultimate target of thalamic fibers (Zhao, Kao, Kanold, 2009; Viswanathan et al. 2017). Thus subplate neurons form a crucial relaye of thalamic activity.

Because after the critical period – when subplate neurons are no longer present – only limited plasticity is present, it is possible that this circuit participates in types of synaptic plasticity that occur only during the critical period. Thus, the disappearance of this circuit might be what ends the critical period.

Our current work focuses on elucidating on how this and other early circuits shape the functional organization of the brain and how these circuits control the critical period (Zhao et al. 2009, Viswanathan et al 2012, Meng et al 2014). Our previous work and the work of others showed that loss of subplate neurons during development leads to severe developmental malformations (Kanold et al., Science 2003, Kanold & Shatz Neuron  2006, Kanold 2009, Tolner et al 2012). To accomplish our goals we use a multi-faceted approach utilizing neurophysiological (electrophysiology and imaging) and molecular techniques as well as computer simulations of the behavior of single neurons and neuronal networks.

Clinical relevance:

Subplate neurons are present in the human cortex during prenatal and early postnatal times, depending on the region of cortex. In fact in the second trimester a large fraction of cortex is occupied by subplate neurons. Subplate neurons are are highly susceptible to injury, especially in the womb. Short episodes of hypoxia (such as occurring during birth!) selectively damage subplate neurons (see here). Such hypoxic episodes in humans are thought to be related to the development of cerebral palsy and other disabilities many of which are associated with aberrant cortical activity. Similarly our work showed that fetal exposure to VPA, which is linked to the autism in humans, results in subplate neurons in neonatal animals (Nagode et al. 2017). Thus changes in the cortical circuitry in autism are present from the youngest ages on. Thus learning more about the subplate and its function is important in understanding the origin of neurodevelopmental diseases.

Advertisements